ADP-ribosylation factors (ARFs) constitute a family of small monomeric GTPases. ARFs 1 and 3 function in the recruitment of coat proteins to membranes of the Golgi apparatus, whereas ARF6 is localized to the plasma membrane, where it appears to modulate both the assembly of the actin cytoskeleton and endocytosis. Like other GTPases, ARF activation is facilitated by specific guanine nucleotide exchange factors (GEFs). ARNO (ARF nucleotide-binding site opener) is a member of a growing family of ARF-GEFs that share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7p, and a C-terminal pleckstrin homology domain. Recently, ARNO and its close homologue cytohesin-1 were found to catalyze in vitro nucleotide exchange on ARF1 and ARF3, respectively, raising the possibility that these GEFs function in the Golgi. However, the actual function of these proteins may be determined in part by their ability to interact with specific ARFs and in part by their subcellular localization. We report here that in vitro ARNO can stimulate nucleotide exchange on both ARF1 and ARF6. Furthermore, based on subcellular fractionation and immunolocalization experiments, we find that ARNO is localized to the plasma membrane in mammalian cells rather than the Golgi. It is therefore likely that ARNO functions in plasma membrane events by modulating the activity of ARF6 in vivo. These findings are consistent with the previous observation that cytohesin-1 regulates the adhesiveness of ␣L␤ 2 integrins at the plasma membrane of lymphocytes.

Life expectancy is rising, which is increasing the demand for endoscopic retrograde cholangiopancreatography (ERCP) in the elderly. Little data, particularly on complex procedures, has been reported. In this study, we compare the differences in the success and complications in ERCP between patients older and younger than 80 years old. We used a large endoscopic database reviewing the ERCPs performed and 30-day complications addressing age, degree of difficulty of procedures, and complications. A total of 2,606 patients underwent 3,924 ERCPs. Six hundred and twenty-eight were octogenarians undergoing 728 procedures. Mean age was 83.5 years in the octogenarian group and 59.0 years in the younger group. The endoscopic success rate was lower in octogenarians (96.9 vs. 98.3%, P = 0.004). Overall, complication rates between both groups was significantly less in older compared to younger patients (1.64 vs. 3.50%, P = 0.006). Complication and failure rates were higher as procedure complexity increased in all patients. ERCP in the elderly carries a high degree of success with low complication rates. Elderly patients carry similar risks of bleeding and perforation and a lower risk of pancreatitis.

The use of a modified coaxial guiding needle and biopsy gun is a simple, safe, and effective method for obtaining tissue from thyroid nodules and is applicable to sampling other superficial masses as well.

No abstract